The University of Rochester Medical Center has targeted X-ray crystallography as an area for strategic development due to its potential for high impact on existing NIH-funded research programs and Centers. A limiting factor in this plan is that our current X-ray instrumentation is between 12 and 14 years old. As such, the equipment is prone to frequent service failures, costly maintenance, and lacks a robust mechanism to provide access to non-specialists. As part of a cost-sharing plan to establish a state-of-the-art, shared X-ray core facility, we request funds to replace our aged system with a modern, higher-throughput instrument. If funded, the Medical Center administration will leverage this support by infusing additional funds that provide for a PhD-level facility manager, as well as maintenance fees, to assure shared core accessibility and functionality for a period of five years. A group of seven major core users has already been identified who have crystals in hand and require instrument access - a regional user from the nearby Rochester Institute of Technology also has crystals. In the planning stages, our tests indicated that the Bruker AXS I?S microfocus sealed tube X- ray source, integrated optics, APEX II CCD detector, Oxford 700 cold stream and motorized goniometer head (for rapid sample centering) mounted on a 4-circle platform would accelerate user throughout by five-fold or more compared to our current in-house system. The 0.120 mm beam size produced by Bruker's multilayer Quazar optic is well suited for rapid screening of small crystals, which are typical of most experiments. The proposed system was also capable of handling a 295 [unreadable] unit cell edge in tests. Significantly, the routine maintenance needs of the Bruker AXS system are relatively modest, and its service contracts are nearly fifty percent lower than our existing equipment. By increasing throughput and expanding the scope of user accessibility, we are confident that the proposed shared X-ray core will significantly enhance the competitiveness of current NIH-funded research projects. This shared resource will be integrated with the research goals of existing Cores and Centers, such as the Developmental Center for AIDS Research, the High Throughput Screening (HTS) Core, and The Center for RNA Biology: From Genome to Medicine. Such Centers represent forums of targeted research that unite clinical and basic researchers who are waging a war to improve public health. HEALTH RELEVANCE: X-ray crystallography is a valuable technique to visualize biological molecules and to understand their mechanisms of action in relation to human disease. The crystallography instrumentation at the University of Rochester is 12-14 years old, which impedes our ability to make new discoveries and hampers access by our scientists. We request a state-of-the-art system that will be maintained as a shared resource, and integrated with the goals of our existing NIH-funded strategic Centers whose primary mission is to improve public health.